Abstract
BackgroundHepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined.MethodsThe expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay.ResultsVimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells.ConclusionTaken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment.34DcRyoit96E3KKn7g7GiGVideo abstract
Highlights
Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC)
You et al Cell Commun Signal (2021) 19:33. Taken together, these findings demonstrate that, dependent on LIM and SH3 domain protein 1 (LASP1), vimentin is crucial for HBXmediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment
HBV X protein (HBX) upregulates vimentin protein expression to facilitate EMT of hepatoma cells To explore the effect of HBX on EMT, we constructed the hepatoma cells stably transfected with HBX (Fig. 1a)
Summary
Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Extensive studies have expanded our understanding of the functions of HBX in the pathogenesis of HCC [6], the molecular mechanisms associated with the progression of the tumor mediated by the viral protein are still not well clarified. Epithelial-mesenchymal transition (EMT) is a significant event in the development of HBV-associated HCC [7]. HBX has been reported to induce the EMT phenotype in hepatoma cells [8,9,10,11], with the decreased levels of epithelial cell–cell adhesion molecule E-cadherin, while the increased expressions of cytoskeletal actin component β-catenin and vimentin. Whether vimentin participates in the dysfunction of hepatoma cells mediated HBX, and the molecular mechanisms associated with vimentin expression mediated by HBX are not clear
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